Trainee Lightning Talk: Gabrielle Grifno

Mosaic pattern: lung function heterogeneity evolves with age at the alveolus level

ABSTRACT

Objectives: Inhaled particles with significant public health relevance include: (i) airborne pathogens (viruses, bacteria), transported as respiratory droplets, (ii) pollutants in urban andoccupational settings such as microplastics and smoke, and (iii) inhalation-based therapeuticsand diagnostics. However, aerosol dynamics during active breathing at the alveolar scale arepoorly understood due to low spatial or temporal resolution of clinical and histological methods, respectively. We applied our crystal ribcage platform (Nat. Methods, 2023) to probe dynamic aerosol transport in functional lungs during breathing. Surprisingly, we found that aerosols distribute in a heterogeneous age- and material-dependent “mosaic” pattern where only discrete clusters of alveoli receive droplets.

Methods: Lungs (mouse, pig, human) were imaged inside the crystal ribcage using ultrafast microscopy during dynamic aerosol inhalation. Alveolar heterogeneity was probed for particles of variable mass including small molecules (0.5, 70 kDa), nanoparticles (200 μm), bacterial pathogens (1 μm), microplastics (1-5 μm).

Results: We used the crystal ribcage to directly probe aerosol distribution in alveoli during physiological breathing for the first time (A). Aerosols deposited in a geometric “mosaic pattern”, where some alveoli received many droplets, forming “tile”-like clusters, while adjacent alveoli in “bands” between tiles had no deposition (A-B). Across the lung lifetime, the number of alveoli inside tiles grew 3-fold larger than in the bands (C D). The mosaic pattern was observed in porcine and human lungs (B), and across variable aerosolized materials (E). Lastly, aerosol redistribution post deposition decreased with increasing particle size and age (E-G). These findings suggest that normal lung biology is heterogeneous due to differential distribution of inhaled particles and potentially gasses over the lung lifetime. Mosaic pattern heterogeneity also implies that respiratory mechanics influence postnatal lung development to a degree that was previously unknown. These data can be leveraged to inform public health strategies and optimize inhaled therapeutics.

Gabrielle N. Grifno*1, Han Kahvecioglu1, Victoria Travnik1, Rohin Banerji1, Béla Suki1, Hadi
T. Nia1
1Department of Biomedical Engineering, Boston University